CPn infection promotes transmigration of monocytes through human brain endothelial cells

Chlamydophyla (chlamydia)pneumoniae in the AD brain More work by Brian Balin. Once again we see very good evidence of CPn being a neural pathogen.

Chlamydia pneumoniae in the alzheimers brain This work is on AD but the authors discovered CPn in the cells of the brain near the AD plaques. This should help establish CPn as a potentially neural pathogen

-Chlamydia pneumoniae in the Alzheimer's brain varies with APOE genotype The APOE genotype apparently interacts with CPn in alzheimers patients carrying that genotype. This suggests an interesting theory: that a bacteria is not the same in every person in terms of effects but rather an interaction between genes and bugs results in the pathology an individual experiences. This is a whole new understanding of how we interact with our environment.

The Balin research related to CPn in Alzheimer's Disease This list of research abstracts with links is an important study for anyone interested in CPn in the brain. Of note, this researcher like Dr Sriram also finds CPn in the brain consistently when others do not. This is likely due to the fact that both VU and Balin use frozen, not formalin fixed, tissue.

High prevalence of CPn antibodies in vascular dementia While VD is not alzheimers it is another indication that CPn has an affinity for cerebral tissue and is related to loss of brain integrity

Doxycycline versus doxycycline and rifampin in undifferentiated spondyloarthropathy, with special reference to chlamydia-induced arthritis a; 9 month studyA combinaiton protocol is effective here vs a monotherapy.

-Antibiotic treatment of arthritis Osteoarthritis when treated with doxycycline has significantly reduced joint space narrowing 40% better than controls.

Persisitant CPn and Arthritis Great paper overviews the concept of CPn and C. trachomatis as causitive agents in arthritis.

Sjogren's and CPn

Burden of infection and insulin resistance in healthy middle aged men This paper finds inflammation and infection related to blood glucose
Cpn in "wet" macular degeneration This article in the lay press details new findings that CPn is responsible for the inflammation seen in AMD. The abstract of the actual research is HERE

Behcets may be CPn related. A disease traditionally thought to be autoimmune is found to have significant titers of CPn.

-Cpn in prostate pathology This research found CPn in prostates with pathology. It even offers the theory that patholgy from hypertrophy to cancer represents different stages of infection.

-Chlamydia Pneumoniae in Interstitial Cystitis Is IC a mystery disease or is it a bacteria? This paper outlines the results of research investigating this.

Interstitial cystitis and CPn Link out to paper on this subject.

Chlamydia pneumoniae and Rosacea

Int Immunopharmacol. 2008 Sep;8(9):1239-47. Epub 2008 May 22

Modulation of cytokine and beta-defensin 2 expressions in human gingival fibroblasts infected with Chlamydia pneumoniae.

Rizzo A, Paolillo R, Buommino E, Lanza AG, Guida L, Annunziata M, Carratelli CR. Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, Faculty of Medicine and Surgery -Second University of Naples, Naples, Italy. Human beta-defensin 2 is an antimicrobial peptide that is produced by several epithelial cells after stimulation with micro-organisms and inflammatory mediators. Gram-negative bacteria, which are typically detected in periodontal pockets in periodontitis, elicit a stronger antibacterial peptide response of human beta-defensin 2 by epithelial cells. In this study, we investigated whether Chlamydia pneumoniae is able both to enter and grow in human gingival fibroblasts (HGF), to modify the production of cytokines, and is involved in regulation of beta-defensin 2 expression. Gingival fibroblasts discarded from periodontal procedures on healthy young individuals were infected with viable C. pneumoniae or with heat- or ultraviolet-inactivated organisms at a multiplicity of infection of 4 inclusion-forming units per cell. Our results demonstrate that after 48 h of incubation with viable C. pneumoniae, gingival fibroblasts showed a proliferative response as seen by both colorimetric assay and direct cell count (40% and 45%, respectively). Moreover, cells incubated with viable or ultraviolet light-inactivated C. pneumoniae organisms showed an increase in the levels of interleukin-6, interleukin-10 and human beta-defensin 2 in a time-dependent fashion, while the cells infected with heat-killed bacteria did not show a significant production either of the cytokines or beta-defensin 2 at any time. In conclusion, we demonstrate the correlation between multiplication of C. pneumoniae in human gingival fibroblasts and release of interleukin-6, interleukin-10 and up-regulation of beta-defensin 2, suggesting that gingival fibroblasts may be a periodontium niche for obligate intracellular C. pneumoniae and may play a role in innate gingival immune system and inflammatory response mechanisms of periodontitis.

 Microbes Infect. 2008 Jun 29. [Epub ahead of print]

Chlamydia pneumoniae infection results in generalized bone loss in mice.

Bailey L, Engström P, Nordström A, Bergström S, Waldenström A, Nordström P. Department of Molecular Biology, Umeå University, SE-90187, Umeå, Sweden. Osteoporosis is associated with a general bone loss. Whether infections could contribute to osteoporosis is not known. Chlamydia pneumoniae causes chronic infections and produces potentially bone resorptive cytokines. The effect of C. pneumoniae infection was investigated in vivo in 10-week old mice (c57BL/6) and in vitro in the human osteoblast-like cell line hFOB 1.19 (hFOB). Bone mineral density (BMD) was measured before and 16 days after infection. C. pneumoniae-infected mice had decreased (p<0.05) total and subcortical BMD at the distal femur and proximal tibia compared with controls, but no body-weight gain differences. IL-6 (56 vs. 39pg/mL, p=0.02) and IL-1beta (11 vs. 0pg/mL, p=0.003) levels in sera, and CD3(+) T-cells (p=0.04) were higher in infected mice compared with controls. In vitro, hFOB infected with C. pneumoniae was associated with increased IL-6 (p=0.01) and RANKL (p<0.05) mRNA expression; additionally, IL-6 secretion increased in a dose-dependent manner (p<0.05). In summary, mice infected with C. pneumoniae had generalized bone loss associated with increased IL-6 and IL-1. In addition, C. pneumoniae established an infection in an osteoblast cell line in vitro with similar cytokine profiles as those in vivo, supporting a causal linkage.

 Cpn has been linked to obesity and weight gain, obviously an area of great interest. This is the first piece of research to reveal more about the possible mechanisms: inflammation (suprise, suprise) and impaired insulin signaling. J Infect Dis. 2008 Feb 1;197(3):439-48.Links

Chlamydophila pneumoniae inhibits differentiation of progenitor adipose cells and impairs insulin signaling.

Shi Y, Liu Y, Murdin A, Raudonikiene-Mancevski A, Ayach BB, Yu Z, Fantus IG, Liu PP. Toronto General Hospital Research Institute, Toronto, Ontario, Canada. BACKGROUND: Recent clinical studies have shown Chlamydophila pneumoniae seropositivity to be related to overweight status and inversely related to insulin sensitivity. The present study was performed to investigate the potential effects of C. pneumoniae infection of adipocytes. METHODS: 3T3-L1 cells and primary epididymal preadipocytes were infected with C. pneumoniae either before or after induction of differentiation, and the effects on adipogenesis and insulin signaling were determined. Tumor necrosis factor (TNF)-alpha signaling was examined by assessing the effects of C. pneumoniae infection in preadipocytes isolated from epididymal adipose tissue of both wild-type and TNF-alpha(-/-) mice. RESULTS: C. pneumoniae successfully infected both undifferentiated and differentiated 3T3-L1 cells in vitro. The bacteria were also detected in adipose tissue of infected low-density lipoprotein receptor-deficient mice. TNF-alpha protein levels were significantly increased in cells infected with either live or heat-killed C. pneumoniae or treated with lipopolysaccharide or heat-shock protein 65; this increase was associated with inhibition of adipocyte differentiation and down-regulation of insulin-stimulated tyrosine-phosphorylated insulin receptor and its substrate. In contrast, C. pneumoniae infection in TNF-alpha(-/-) adipocytes produced no apparent changes, but addition of recombinant TNF-alpha reversed this effect. CONCLUSIONS: We demonstrate for the first time that C. pneumoniae can infect murine pre- and postdifferentiated adipocytes and, through a TNF-alpha-mediated inflammatory mechanism, can impair differentiation and insulin signaling.

This is a quite excellent review by Dr. Nicholson published in a mainstream peer reviewed scientific journal. He gathers together a considerable breadth of the research available on infectious sources of these diseases while being even handed in acknowledging the lack of scientific concensus and negative findings. Dr. Nicholson has been a leading researcher in the infectious paradigm for a number of illness, especially CFIDS and Gulf War syndrome.  Chronic Bacterial and Viral Infections in Neurodegenerative and Neurobehavioral Diseases Garth L. Nicolson, PhD(Department of Molecular Pathology, The Institute for Molecular Medicine, Huntington Beach, CA) LABMEDICINE

This is the research that we have relating Chlamydia pneumoniae to CFS and Fibromyalgia:

-Cpn in Chronic Fatigue -This work supports the above work in CFS and cryptic organisms. This time done by researchers in California.

-Infections and Fibromyalgia- If you are using or prescribing this treatment, please read this paper. It overviews the idea of infectious causes for chronic illness and is excellent.

The General Information Page:

CPn Epidemiology Epidemiology means the study of how often and where a germ crops up.

Early events in CPn infection of host cells Short pubmed abstract.

Pharmacodynamics of Antichlamydials This paper addresses the issues of various lifecycles and pharmacodynamics. It is very clear that various agents are needed to eradicate CPn. Link out. Whole citation.

Chlamydiae.com link This site has tremendous technical information about CPn

Slides for a powerpoint slide presentation by Charles Stratton on Cpn.

Chlamydia pneumoniae: crossing the barriers? This long paper is included in totality. It addresses the issue of how CPn crosses epithelial barriers, causes inflammation and how it invades and parasitizes cells. A must read for the physician contemplating using this approach. Provides background.

Research by Charles Stratton and co-researchers This is a simple list of the finished work, includes a link to a complete list. Much of this relates to MS.

Cpn in chronic diseases This is a link out to work that overviews the main issues in CPn in chronic illness. A must read for the serious investigator.

Preliminary report on Wheldon/Stratton case studies This report outlines the theory and usefulness of metronidazole being added to the CPn protocol.

Persistent Chlamydial Envelope antigens This paper describes finding that chlamydia trachomatis can continue to induce inflammation well after treatment. This indicates that persistence of inflammation may well be a feature of CPn infection.

Review: Bacterial host Interactions This review of material relating to bacteria and how persistent infections may be supported by faulty mechanisms inside the idividual body is a must read. Somehwat technical, it's in depth look at the current research regarding this subject is essential for understanding that persistence is well recognized even if clarity about just exactly how it happens is just beginning.

Potential Role of Infections in Chronic Inflammatory Disease This self explanatory title names a referenced opinion paper written by a medical researcher and professor. It is a PDF file.

PCR analysis of CPN This technical paper is a must for the professional and interested techies. How can it be some say it's there and other researcher say it's not? The answer is here.

-Results, and Clinical Performance of Five PCR Assays for Detecting Chlamydia pneumoniae DNA in Peripheral Blood Mononuclear Cells A must read for the interested person interested in the technical details of finding these cryptic bacteria. You must understand this if the research that is done using other tests which find no relationship to CPn is to be properly understood.

Comparison of Five Serologic Tests for Diagnosis of Acute Infections by Chlamydia pneumoniae Another page with 5 tests being compared this one from 2000. Full citation available.

MS is covered in this page. Please read more from the other research pages also as it is the whole picture that makes it compelling not just what is here....

A review of PCR in CPn infection by David WheldonThere are many studies on MS using the PCR to look for CPn. this review by David Wheldon is insightful

Chlamydia Pneumoniae infection in Neuronal cells lines

CPn respiratory infection associated with relapse in MS

Annotation by Marie with links on nitric oxide CPn and MS

Nitric Oxide and CPn: Multiple sclerosis link?

CPn infection induces transmigration of monocytes through human brain epithelial cells This work was undertaken to see if CPn might transmigrate because there is some work associating CPn with AD. Once you see that it can migrate across the BBB and that it can infet microglia and brain cells, is it such a leap to imagine it could cause MS?

Detection of chlamydial bodies and antigens in the central nervous system of patients with multiple sclerosis The newest published research on CPn in MS released October 1 2005. This work used several methods for detection of CPn in these MS patients, proving this work to be very thorough and extremely convincing. Many others have "tried" to find CPn using one method such as PCR, but his work also reaffirmed the assertion that CPn was present with other approaches as well.

-Pilot study to examine the effect of antibiotics on MRI outcomes in RRMS This is the most recent research to read if you are interested in MS and CPn. This study was small but it highlights interesting points about the reaction of the MS brain to antibiotic treatment.

The clinical response to minocycline in multiple sclerosis is accompanied by beneficial immune changes: a pilot study. This study was looking at minocin as an imunomodulatory agent but the positve responses in terms of gad enhancing lesions and relapses makes a person consider that there is likely more than one reason to do CAPs.

-Assoc. of Chlamydia pneumonie with nervous sytem disease This paper is a must read if you have MS.

Chlamydia pneumoniae infection of microglial cells Very important paper. Please read.

CSF molecular demonstration of CPn DNA is associated with cinical and brain magnetic resonance in RRMS This paper from 2004 shows that several neurolgoical diseases are associated with evidence of CPn in the brain, but also indicates that active disease of MS has a higher association. Importantly taken with Balin's work on AD we are beginning to see a neurological pathogen that possibly causes several kinds of brain pathologies. Since we know other germs like staph has the same kind of differing presentations, is that really so odd?

Epidemiologic Evidence for MS as an infection- J F Kurtzke Classic important paper. Kurtzke is clear that an infectious agent is to blame for MS. This in depth report includes an immene amount of data on the Faroese.

Asthma and Infections,

Seroprevalence of CPn infections in otolaryngeal infections

Mechanisms of chlamydiophilia mediated GM-CSF release in HUman Bronchial cellsHow does CPn tirgger inflammatoin in lung tissue? this attempts to pinpoint the answer

Serum IgG and IgA antibodies to CPn in EmphysemaThis article indicates that serology is positive in emphysema and that clinical course and worsening is tied to CPn status

Asthma and CPn. Explains interaction of patient immune system with the CPn. Technical.

-Cpn in recurrent respiratory infections This work with children with recurrent respiratory infections indicates that treating for cryptic bacteria improves outcomes. Treatment was prolonged due to the nature of cryptic, or "atypical" bacteria.

Chlamydia Pneumoniae and COPD This reserach indicates that acute exacerbations of COPD re associated with CPn.

-Cpn in asthma This research indicates that cryptic bacteria play a role in asthma. Outcomes were improved by adding abx.

1: Respir Res. 2008 May 30;9:48.

Severe asthma exacerbation: role of acute Chlamydophila pneumoniae and Mycoplasma pneumoniae infection.

Cosentini R, Tarsia P, Canetta C, Graziadei G, Brambilla AM, Aliberti S, Pappalettera M, Tantardini F, Blasi F. Emergency Medicine Department, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Gruppo NIV Policlinico, Milan, Italy. r.cosentini@gmail.com BACKGROUND: Chlamydophila pneumoniae and Mycoplasma pneumoniae are associated with acute exacerbation of bronchial asthma (AEBA). The aim of this study was to evaluate the correlation between these acute bacterial infections and the severity of AEBA. METHODS: We prospectively analysed consecutive patients admitted to the Emergency Department with acute asthma exacerbation. In every patient peak expiratory flow (PEF) measurement was performed on admission, and spirometry during follow-up. Serology for Chlamydophila and Mycoplasma pneumoniae was performed on admission and after 4-8 weeks. RESULTS: Fifty-eight patients completed the study. Acute atypical infections (AAI) was observed in 22/58 cases; we found single acute C. pneumoniae in 19 cases, single acute M. pneumoniae in 2 cases, and double acute infection in one case. Functional impairment on admission was greater in patients with AAI than in patients without AAI (PEF 205 +/- 104 L/min vs 276 +/- 117 p = 0.02) and persisted until visit 2 (FEV1% 76.30 +/- 24.54 vs FEV1% 92.91 +/- 13.89, p = 0.002). Moreover, the proportion of patients who presented with severe AEBA was significantly greater in the group with AAI than in the group without AAI (15/22 vs 12/36, p = 0.01; OR 4.29, 95% CI 1.38-13.32). CONCLUSION: Our data suggest an association between acute atypical infection and a more severe AEBA.

CPn and Cardiovascular Issues -

Statins and CPn

Persistent CPn infection of cardiomyocytes associated with acute MI

Atherothrobotic events and CPn Long term study on CPn IgG and IgA findings in atherothrombosis

Higher incidence of persistent chronic infection of Chlamydia pneumoniae among coronary artery disease patients in India is a cause of concern.

CPn and atherosclerosis Article which is in depth and includes many interesting diagrams and pictures. An overview of the understanding of the role CPn plays in cardiovascular issues with many links in the work

Experimental Chlamydia pneumoniae infection model: effects of repeated inoculations and treatment This article is about mice repeatedly infected with CPn and the impact on the cardiovascular system. luteolin in mentioned.

The role of endothelial dysfunction and Chlamydia pneumoniae infection in patients with ischemic stroke Intimal thickness is a measure of atherosclerosis this research correlates it with CPn seropositivity

Cpn in heart disease Think all this research is done by one or two people? Not at all. This link out highlights work done in Seattle on several cryptic organisms in CFS.

Doxycycline use and incidence of CAD This retrospective study of clients in a Greek cardiac practice reviewed use of doxy and later incidence of CAD. A reduction was seen.

The CDC on CPn The centers for disease control recognizes CPn as an emerging issue in atherosclerosis and other diseases. Once again CPn is becoming more recognized in chronic illness traditionally thought "autoimmune"

The Influence of CPn on aortic stiffness in healthy young menIs CRP a response to CPn in cardiovascular issues? C reactive protein and pulse wave velocity measurement of stiffness were both statistically higher in the IgA positive group for CPn.

Antibodies to 60-kilodalton heat shock protein and outer membrane CPn in people with CAD (coronary artery disease) Again, if you have CAD you have antibodies to the various proteins of CPn.

Autoimmunity to human heat shock protein 60, CPn infection, and inflammation in predicting coronary artery riskAutoimmunity plays a role in CPn infection

Antibody respose to Chlamydial heat shock protein strongly associated with cornoary artery disease HSP's are a contributing factor in CPn disease in study after study.

Serological evidence of CPn LPS antibodies in atherosclerosis of various vascular regions There are several proteins associated with CPn tht are immunogenic.

Chronic CPn infection associated with serum lipid profile known to be a risk for CAD CAD is coronary artery disease

Elevated antibody levels against Chlamydia pneumoniae, human HSP60 and mycobacterial HSP65 are independent risk factors in myocardial infarction and ischaemic heart disease. How have we missed this for so long?

Synergistic effect of persistent Chlamydia pneumoniae infection, autoimmunity, and inflammation on coronary risk. Several factors at work accounting for the research into other risk factors.

Chlamydial and human heat shock protein 60 homologues in acute coronary syndromes. (Auto-)immune reactions as a link

Effect of chronic Chlamydia infection with non-specific inflammation on cardiovascular complications in acute myocardial infarct

Azithromycin for the secondary prevention of coronary events Azithromycin alone, a bacteriostatic agent, is incapable of ridding the body of CPn. The EB's are not touched by this drug, the cryptic and peristant forms are encouraged, and it's bacteriostatic nature means the bacteria simply stop actively replicating and metabolizing until the coast is clear. You cannot create any meaningful research into this subject until you account for all lifecycle forms. We are essentially dealing with a form of resistance here. The conclusion of this study was that azith did not decrease coronary events.

Effect of prolonged treatment with azithromycin, clarithromycin, or levofloxacin on Chlamydia pneumoniae in a continuous-infection model This paper finds that treatment with standard chlamydia effective antibiotics does not eradicate persistence. This highlights the need for combination and very long term treatment if one wishes to eradicate CPn.

Azithromycin therapy in patients with chronic Chlamydia pneumoniae infection and coronary heart disease: immediate and long-term This one indicated a possibly positive outcome on fibrinolysis though again the azith did not impact CPn positivity. Taken with the abstract above we have a situation that is confusing to the clinician - until you understand the pathogen and it's lifecycle. Then these studies are clearly incomplete and therefore inconclusive.

The final report on the ROXIS study This paper outlines the ROXIS study on roxithromycin use in patients who had experienced an acute non q wave coronary problem. The folow up reposts a positive effect. This links to the whole citation.

Effect of Treatment for Chlamydia pneumoniae and Helicobacter pylori on Markers of Inflammation and Cardiac Events in Patients With Acute Coronary Syndromes
Another antibiotic study with positive results though serologic markers of CPn and H pylori were not affected by treatement. It might be suggested this means it was some other aspect of the abx that influenced the disease (ie antiinflammatory) but since persistent CPn is not reflected in serologic markers it is likely moot. The whole citation is linked here.

Heat-shock protein 60-reactive CD4+CD28null T cells in patients with acute coronary syndromes We can certainly recognize how that crafty CD4+CD28 combo from MS shows up in this cardiac study and also in RA, somehow researchers from different fields don't seem to recognize them yet as possibly caused by the same source CPn, not autoimmunity.

Fulminant carditis and CPn This is a case of carditis that turned out to be CPn and CP together.